REgulatory T Cell Therapy to Achieve Immunosuppression REduction
ConditionKidney Transplantation
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-65
SponsorSingulera Therapeutics Inc.
About this trial
The goal of this multi-national, multi-center, open-label, randomized Phase 2 trial is to determine the safety and efficacy of administering expanded regulatory T cells (TRK-001) to prevent allograft rejection in living donor renal transplant recipients.
Enrolled subjects will be randomized to one of 2 study arms:
Arm 1 subjects will receive standard of care immunosuppression
Arm 2 subjects will receive initial standard of care (SOC) immunosuppression and a single infusion of TRK-001. Three months after the transplant, Arm 2 subjects may be able to begin reducing their immunosuppression medication to a 1-drug regimen.
The primary outcome measures of trial are to evaluate several components indicating immunologic problems with the transplanted organ at 1-year post-transplant and to evaluate the ability for the study subjects given TRK-001 to wean to a 1-drug immunosuppression regimen.
All enrolled subjects will be followed for 5 years post-transplant.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Males or females aged 18-65 years as of the date of informed consent who will undergo a single organ, living donor kidney transplant.
Donor aged 18-65 years as of the date of organ donation. A certain degree of HLA matching between the donor and the recipient is not required.
Blood type compatibility between recipient and donor must be established as follows.
No prior organ transplant of any kind.
Disqualifiers
Known sensitivity or contraindication to thymoglobulin, everolimus, sirolimus, or tacrolimus or other immunosuppression medication prescribed.
Subjects with a positive crossmatch by virtual cross matching or complement-dependent cytotoxicity (CDC) cross matching or flow cytometry cross matching (FCXM).
Subjects with PRA >80% per SOC pre-transplant assessment. PRA must be repeated prior to transplant if patient receives a blood product transfusion after the initial assessment.
Subjects with current or historic donor specific antibodies.
Trial design
Design model
Parallel
Treatments tested in this trial
Arm 1: SOC (mTOR + CNI)
DrugSubjects randomized to Arm 1 will remain on standard dual-immunosuppression therapy (CNI and mTOR) throughout the trial.
Arm 2A: TRACT/MONO mTOR
Biological/VaccineAll subjects will be prescribed standard of care (SOC) immunosuppressive agents. Subjects randomized to Arm 2 will be maintained on the prescribed SOC immunosuppression (tacrolimus + sirolimus or everolimus) and have a single intravenous infusion of autologous, expanded Tregs (TRK-001) at Day +53 to +67 post-transplant. At Month 3 post-transplant, Arm 2 subjects will be further randomized to receive either: * Arm 2A: mTOR monotherapy or * Arm 2B: CNI monotherapy. These subjects will transition to the assigned 1-drug immunosuppression regimen beginning at Month 3 post-transplant. Weaning must be completed by 12 months post-transplant. Subjects in Arm 2 will undergo leukapheresis to collect peripheral blood mononuclear cells required for the cellular product.
Arm 2B: TRACT/MONO CNI
Biological/VaccineAll subjects will be prescribed standard of care (SOC) immunosuppressive agents. Subjects randomized to Arm 2 will be maintained on the prescribed SOC immunosuppression (tacrolimus + sirolimus or everolimus) and have a single intravenous infusion of autologous, expanded Tregs (TRK-001) at Day +53 to +67 post-transplant. At Month 3 post-transplant, Arm 2 subjects will be further randomized to receive either: * Arm 2A: mTOR monotherapy or * Arm 2B: CNI monotherapy. These subjects will transition to the assigned 1-drug immunosuppression regimen beginning at Month 3 post-transplant. Weaning must be completed by 12 months post-transplant. Subjects in Arm 2 will undergo leukapheresis to collect peripheral blood mononuclear cells required for the cellular product.
Treatment groups
34 Participants
are divided into 3 treatment groupsGroup A: Arm 1: Standard of Care (SOC)Active comparator 1 intervention
Group B: Arm 2A: TRACT/MONO mTORExperimental treatment 1 intervention
Group C: Arm 2B: TRACT/MONO CNIExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Development of de novo donor-specific antibodies
A primary outcome measure for this study is to evaluate a composite endpoint of immunologic events against the allograft, where a failure is defined as patient-experienced immunologic events including the development of de novo donor-specific antibodies.
Time frame
Month 12 Post-transplant2
Biopsy-proven acute rejection
A primary outcome measure for this study is to evaluate a composite endpoint of immunologic events against the allograft, where a failure is defined as patient-experienced immunologic events including biopsy-proven acute rejection.
Time frame
Month 12 Post-transplant3
Biopsy-proven subclinical rejection
A primary outcome measure for this study is to evaluate a composite endpoint of immunologic events against the allograft, where a failure is defined as patient-experienced immunologic events including biopsy-proven subclinical rejection.
Time frame
Month 12 Post-transplant4
Development of significant (2+) interstitial fibrosis/tubular atrophy
A primary outcome measure for this study is to evaluate a composite endpoint of immunologic events against the allograft, where a failure is defined as patient-experienced immunologic events including the development of significant (2+) interstitial fibrosis/tubular atrophy.
Time frame
Month 12 Post-transplantSecondary outcomes
1
Successful maintenance of monotherapy (Arm 2)
A secondary outcome measure for this study is to evaluate the ability for Arm 2 subjects to successfully maintain monotherapy through two-years post-transplant.
Time frame
Month 24 Post-transplant2
Development of de novo donor-specific antibodies
A secondary outcome measure for this study is to evaluate overall and composite component-specific time to immunologic failure where a failure is defined as patient-experienced immunologic events including the development of de novo donor-specific antibodies.
Time frame
To Month 60 Post-transplant3
Biopsy-proven acute rejection
A secondary outcome measure for this study is to evaluate overall and composite component-specific time to immunologic failure where a failure is defined as patient-experienced immunologic events including biopsy-proven acute rejection.
Time frame
To Month 60 Post-transplant4
Biopsy-proven subclinical rejection
A secondary outcome measure for this study is to evaluate overall and composite component-specific time to immunologic failure where a failure is defined as patient-experienced immunologic events including biopsy-proven subclinical rejection.
Time frame
To Month 60 Post-transplantSponsors and contacts
Click on the lead sponsor to view all of their trials.
Singulera Therapeutics Inc.
Lead sponsor
Taiwan Bio Therapeutics Inc.
Collaborator
Source ClinicalTrials.gov